Diabetes is associated with an increased risk of atherosclerosis, with the blood platelet possibly involved. Platelets from diabetic subjects may show enhanced sensitivity to ADP, epinephrine or collagen, and both plasma factors and an intrinsic platelet sensitivity have been reported. However, the biochemical basis for the hyperreactivity is not clear. Plasma-membrane glycoproteins are likely candidates, since these serve as receptors for platelet aggregating agents such as ADP and thrombin. The proposed feasibility study will test the hypothesis that abnormal function of platelet glycoproteins occurs in diabetes. Platelet-rich plasma from diabetics known to possess hyperaggregable platelets will be compared with matched controls. Plasma-membrane glycoproteins will be surface labelled with radio isotopes either before or after selection of platelet groups of differing sensitivity to ADP or other aggregating agent. In separate experiments platelets will be exposed to (32P) to label their glycoproteins internally. Gel electrophoresis of solubilized membranes will then allow analysis for protein, glycoprotein and radioactivity content in the four major glycoprotein bands. Attention will focus on potential changes in one or all of these bands. For the (32P) experiments in particular, alterations in high-molecular weight aggregates will be analysed, since preliminary results of others suggest cluster formation of membrane components may be involved in triggering platelet function. Finally, levels of cyclic AMP and platelet membrane cholesterol will be examined in the diabetic and control groups, since these factors have been implicated in the regulation of platelet function via control of protein kinase activity.